This application is for an NIMH Research Scientist Development Award. The University of California, San Francisco is the nominating institution and the site of most of the planned research and career development activities. The chief objective of the proposal is to foster the continued development of the Pl as an investigator working at the boundary between molecular human genetics and clinical psychiatry. The proposal is a request for renewal of an existing career development award (a mentored Scientist Development Award), and reflects the progress of the Pl in establishing an independent research program. The PI's laboratory is mainly focused on the use of molecular and population genetics approaches to identify the chromosomal location of genes responsible for bipolar disorder (BP), to clone these genes and then to characterize their function. The proposal outlines these objectives and the plans for achieving them. The new goals represent a natural extension of those enunciated in the current award, and are based on developments in human genetics as a whole, but particularly on work accomplished in athe PI's laboratory during the past four years. Given the rapidity with which human genome mapping is proceeding, it is likely that the tools will be available to permit cloning of BP genes to be completed by the end of the proposed award period. For this reason, the major career development goal of the PI for this period is to prepare to conduct studies aimed at elucidating the function of these genes and their protein products. To facilitate these goals, collaborations have been established with cell and developmental biologists at UCSF. Identifying genes responsible for BP will lead to re-evaluation of the diagnostic categories that are currently in place for mood disorders. Mapping and cloning BP genes will be of great scientific significance and will likely have important implications for clinical practice. Future investigations of clinical implications of BP gene discoveries will be carried out in collaboration with UCSF colleagues. The population genetics studies that are proposed, aimed at understandings the factors governing the detection of linkage disequilibrium and mutational processes of microsatellite loci, will provide information that may be valuable in mapping loci for other psychiatric disorders in addition to BP. These studies will be carried out in collaboration with investigators who have already contributed to the PI's development as a scientist.